title: Apa I polymorphism in the vitamin D receptor gene may affect the parathyroid response in Japanese with end-stage renal disease.
abstract: Vitamin D [1,25(OH)2D3] plays a key role in the pathogenesis of secondary hyperparathyroidism. A polymorphism in the vitamin D receptor (VDR) gene is reported to be involved in bone mineral density and the serum level of intact-osteocalcin (i-OC) in patients with osteoporosis. We investigated the relationship between VDR gene polymorphisms and the levels of intact PTH (i-PTH) and i-OC in 129 Japanese patients with end-stage renal disease (ESRD). The VDR gene sequences were PCR-amplified, and the product was cleaved with the restriction enzymes Bsm I and Apa I. Undigested alleles were designated as B and A, and the digested alleles as b and a, respectively. The frequencies for the Bsm I polymorphism were 0.0% BB, 19.4% Bb, and 80.6% bb, while those for Apa I polymorphism were 14.2% AA, 47.2% Aa, and 38.6% aa. The Bsm I polymorphism of VDR was greatly biased in Japanese people. The i-PTH level in the aa group was about twice as high as those in the both AA group and Aa group (P < or = 0.04). The i-OC concentrations in the aa group was also approximately double those in both the AA group and Aa group (P < or = 0.03). In contrast, no significant differences in age, duration of dialysis, male/female ratio, or the incidence of diabetic nephropathy were observed among these three groups. On the other hand, there was no significant differences in i-PTH and i-OC between the Bb and bb groups. These results suggest that VDR gene polymorphisms can affect parathyroid response in ESRD patients, and the Apa I polymorphism is more informative in Japanese patients than the Bsm I polymorphism. The VDR a gene allele may define the pathogenesis of secondary hyperparathyroidism and of high turnover bone disease in patients with ESRD.
authors.affiliation: Kidney Center, Toranomon Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: T
authors.initials: T
authors.lastname: Shigematsu
authors.forename: T
authors.initials: T
authors.lastname: Tsukada
authors.forename: Y
authors.initials: Y
authors.lastname: Ogura
authors.forename: F
authors.initials: F
authors.lastname: Takemoto
authors.forename: S
authors.initials: S
authors.lastname: Hara
authors.forename: A
authors.initials: A
authors.lastname: Yamada
authors.forename: Y
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: T
authors.initials: T
authors.lastname: Hosoya
mesh_terms: D000483:Alleles; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D007564:Japan; D007676:Kidney Failure, Chronic / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010280:Parathyroid Glands / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000097:blood; D011110:Polymorphism, Genetic; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D015675:Osteocalcin